27 results about "Liraglutide" patented technology

The invention relates to the field of biological medicine preparation, and particularly provides liraglutide precursor peptide tandem recombinant fusion protein, polynucleotide, recombinant expression plasmid, engineered host cell and a method for preparing target polypeptide. The recombinant fusion protein is fusion peptide-target polypeptide-(linker peptide-target polypeptide) n from the N terminal to the C terminal, n is a positive integer from 4 to 6, the fusion peptide is SEQ ID NO.1, the target polypeptide is liraglutide precursor peptide, the linker peptide comprises a spacer peptide and a protease restriction enzyme cutting site, the spacer peptide is SEQ ID NO.2, the isoelectric point of the recombinant fusion protein is 4.6-4.7, and the average hydrophilic value is-0.780--0.765. The proportion of the target polypeptide in the recombinant fusion protein is high, use of solvents under extreme conditions is avoided in the production process, the enzyme digestion efficiency is high, and the product purity and yield are high.

The invention belongs to the technical field of biological medicine, and relates to an oral peptide drug delivery system based on a soybean trypsin inhibitor and core-shell hydrogel, the oral peptide drug delivery system comprises therapeutic polypeptide, KTI and a core-shell structure gel matrix, and the problems that an existing oral peptide delivery system is passively protected and drug burst release is remarkable are solved. A chitosan / sodium tripolyphosphate ionic cross-linked network forms an inner core, a sodium alginate / calcium ion'egg box 'structure cross-linked network forms a shell, and therapeutic polypeptides such as liraglutide and KTI are jointly embedded. Through the pH response characteristic and sequential release design of the core-shell structure, KTI is preferentially and rapidly released in the intestinal environment to inhibit local protease activity, then therapeutic polypeptide is slowly released, and active protection and synergistic interaction are achieved. The invention further provides a specific preparation method and parameters. The polypeptide has the advantages of stable structure in a gastric acid environment, targeted release in intestinal tracts, high encapsulation efficiency, capability of avoiding burst release and the like, and provides a new strategy for efficient delivery of oral polypeptide drugs.

The invention discloses lactobacillus delbrueckii with a muscle protection function in a fat reducing period as well as a product and application thereof, belongs to the technical field of microorganisms, and discloses lactobacillus delbrueckii subsp. Lactis Turb8 with the preservation number of CGMCC No.35627. The lactobacillus delbrueckii subsp. Lactis Turb8 has the advantages that the preservation number is CGMCC No.35627; the strain or the preparation thereof can effectively prevent or improve the accompanying problems of muscle loss and function decline in the process of applying fat-reducing drugs such as GLP-1 receptor agonists (such as liraglutide and semeglutide), and the effect of reducing fat but not reducing muscle is achieved. The strain disclosed by the invention can be used for remarkably increasing the lean body mass ratio of a user, increasing the muscle mass of lower limbs, increasing the cross sectional area of muscle fibers and improving muscle function indexes such as strength of four limbs and suspension endurance while keeping the original weight-reducing effect of a fat-reducing medicine. The invention also relates to microbial agents comprising this strain, various preparations, their use in the preparation of products for ameliorating (in particular drug-induced) muscle reduction.

The disclosure provides compositions for Liraglutide drug substance for intranasal application that meets desired physicochemical stability while maintaining solubility of the active pharmaceutical ingredient for a requisite duration. The present disclosure sets forth examples of a Liraglutide drug substance with various excipients (solvents, preservative, stabilizers, penetration enhancers, complexing agents) to achieve desired product attributes for solubility, stability, and pH.

The present invention relates to specific antibodies and use thereof, such as for identifying and / or quantifying liraglutide fibrils and / or semaglutide fibrils.

A pharmaceutical formulation useful for treating metabolic disorders or conditions is provided, comprising a plurality of particles suspended in a carrier system, the particles (a) having an average diameter based on weight, number, or volume of about 10 nm to about 700 μm, and (b) a solid core comprising at least one glucagon-like peptide-1 receptor agonist or a pharmaceutically acceptable salt thereof, at least partially coated with a coating of an inorganic material comprising a mixture of (i) zinc oxide and (ii) one or more other metal and / or metalloid oxides, wherein the atomic ratio ((i):(ii)) is at least about 1:10 and not more than about 10:1. The mixed oxide-coated particles are preferably synthesized by a vapor-phase coating technique, such as atomic layer deposition. The formulation may provide delayed or sustained release of the glucagon-like peptide-1 receptor agonist for treating metabolic disorders or conditions, such as type 2 diabetes and / or obesity, without a burst effect. The glucagon-like peptide-1 receptor agonist is preferably liraglutide.

The invention belongs to the technical field of biological medicines, and provides application of liraglutide in preparation of a medicine for treating diffuse alveolar hemorrhage and the treatment medicine. The innovative research shows that the liraglutide can be used for treating diffuse alveolar hemorrhage and has an excellent treatment effect, and the brand new treatment thought is convenient in administration, high in safety and low in treatment cost.

The present application relates to a method for removing the main peak residue of liraglutide precursor in a chromatographic column, and the liquid chromatography conditions are as follows: equipment configuration: four-element low-pressure pump or two-element high-pressure pump equipped with flow path switching valve; chromatographic column: InertSil ODS-SP chromatographic column (4.6*250mm, 5um); column temperature: 35-40 DEG C; mobile phase C: sulfate buffer: acetonitrile (82:18), 8M NaOH is adjusted to pH 5.95-6.05; mobile phase D: 50% acetonitrile; flow rate: 1.0ml / min; detection wavelength: 214nm; injection mode: 60% mobile phase D and 40% mobile phase C, isocratic elution for 8min, 0.01M phosphate buffer is injected, 30ul / needle, 1 needle is injected every 8min, a total of 3 needles. The analysis method of the present application can completely remove the main peak residue of liraglutide precursor in the chromatographic column in a short time.

The invention discloses a method for distinguishing biological activities of different GLP-1 analogues. According to the method, liraglutide and semeglutide can be effectively distinguished, tilpotide and HISHS-2001 can be effectively distinguished, accurate matching of treatment requirements, optimization of a medication scheme, promotion of drug research and development and innovation and improvement of clinical medication safety are facilitated, and the application prospect is wide.

A new GLP-1 derivative, which has comparable or better potency, efficacy or efficacy, longer or comparable in vivo duration of action or in vivo half-life, has better or comparable GLP-1 receptor binding affinity, has better or comparable DPP-IV stability, compared to the marketed GLP-1 derivatives such as liraglutide, semaglutide, etc.

The present invention provides an injectable depot composition comprising enavogliflozin and low-dose liraglutide. A combination regimen of enavogliflozin and low-dose liraglutide provides a synergistic effect in the treatment of obesity compared with the single administration of either drug. Furthermore, compared with the single administration of liraglutide, the administered dose of liraglutide can be reduced, and thereby the direct causes of gastrointestinal and cardiovascular side effects of liraglutide can be mitigated. Furthermore, the present invention has the additional advantage of providing an effect for alleviating metabolic diseases and cardiovascular diseases related to blood glucose, blood lipids, blood pressure, fatty liver, and the like through combined administration with enavogliflozin.Furthermore, the depot composition of enavogliflozin and liraglutide according to the present invention can significantly improve treatment convenience and treatment compliance for patients compared to existing liraglutide formulations, which are injected subcutaneously once daily, by unifying the route of administration and increasing the cycle of administration.

The present invention provides an injectable depot composition comprising linagliptin and low-dose liraglutide. The combination therapy of linagliptin and low-dose liraglutide provides a synergistic effect in the treatment of obesity compared to the administration of each drug alone. In addition, the administration dose of liraglutide can be reduced compared to the administration of liraglutide alone, and thus the direct cause of side effects related to the gastrointestinal system and the cardiovascular system of liraglutide can be reduced. Furthermore, by the combination of linagliptin, it has the advantage of additionally providing an improvement effect on metabolic diseases and cardiovascular diseases related to blood sugar, blood lipids, blood pressure, fatty liver, etc. In addition, compared to the conventional liraglutide dosage form of once-daily subcutaneous injection, the depot composition of linagliptin and liraglutide of the present invention can significantly improve patient convenience and patient compliance by unifying the administration route and improving the administration cycle.

This application belongs to the field of genetic engineering technology and discloses human enterokinase light chain mutants and their applications. This application involves single-point mutations or multiple rounds of combined mutations based on the wild-type human enterokinase light chain -C112S mutant sequence. The obtained variants have higher specific activity compared to the parent, which is expected to increase unit yield, reduce the residual amount of protease in the final product, and lower product costs. Furthermore, these mutants exhibit high stability in the enzymatic digestion of peptides / proteases, such as liraglutide and smegglutide, GLP-1 analogs, reducing enzyme usage, increasing digestion efficiency, and decreasing the proportion of non-specific products, thereby lowering the production cost of peptide drugs and promoting the rapid development of related industries.

The invention relates to the technical field of biomedicine, in particular to a nano-composite hirudin protein line capable of remodeling glycolipid metabolism and a preparation method of the nano-composite hirudin protein line. The nano-composite hirudin protein line for remodeling glycolipid metabolism is prepared from the following components in parts by weight: 60 to 85 parts of type I collagen line, 5 to 10 parts of recombinant hirudin, 2 to 5 parts of liraglutide, 1 to 5 parts of ursodesoxycholic acid, 1 to 4 parts of polydopamine and 2 to 5 parts of N-hydroxysuccinimide-polyethylene glycol-maleimide. 2-5 parts of phenylboronic acid modified sodium alginate and 2-5 parts of gallic acid chitosan; according to the invention, on-demand accurate release of drugs in a pathological microenvironment is realized, the intervention efficiency is remarkably improved, the side effects of the system are reduced, meanwhile, a collaborative treatment network is formed, root intervention on complex metabolic disorders is realized, the product can actively remodel a local immune microenvironment while delivering the drugs, the process is controllable, the safety is excellent, and the application prospect is wide. And the benefit of traditional wire embedding weight reduction is greatly improved.

The application relates to the technical field of compound synthesis, in particular to a preparation method of a liraglutide side chain and an intermediate thereof. The preparation method of an intermediate 1 forming a liraglutide side chain comprises the following steps: reacting palmitic acid and HOSU to form a reaction crude product, and crystallizing the reaction crude product to form the intermediate 1, wherein the solvent selected for crystallization is a mixed solvent of ester solvents and alkane solvents, the mass ratio of the ester solvents to the alkane solvents is 1:5-1:10, and the structural formula of the intermediate 1 is The intermediate formed by the preparation method has high yield, high purity and low homologous impurity content, so that the liraglutide side chain formed has high purity and low homologous impurity content, thereby a synthesis method suitable for large-scale production of the liraglutide side chain can be obtained.

The present invention provides for purification of liraglutide using selective ion-pairing agents in the reversed phase-high performance liquid Chromatography, for purifying crude liraglutide from closely related impurities.

The present invention provides an obesity treatment regimen for reducing side effects by low-dose combination administration of linagliptin and liraglutide. The combination therapy of linagliptin and low-dose liraglutide provides a synergistic effect in obesity treatment compared to administration of each drug alone. Furthermore, the administration dose of liraglutide can be reduced compared to administration of liraglutide alone, and thus the direct cause of side effects related to the gastrointestinal system and the cardiovascular system of liraglutide can be reduced. Furthermore, by the combination of linagliptin, it has the advantage of additionally providing an improvement effect on metabolic diseases and cardiovascular diseases related to blood sugar, blood lipids, blood pressure, fatty liver, etc.

The present invention provides a composition for manufacturing liraglutide-containing microneedles that contains liraglutide as an active ingredient, without denaturation of the active ingredient during manufacture, and maintains stability even after manufacture, and liraglutide-containing microneedles with enhanced stability manufactured using the composition. The composition for manufacturing liraglutide-containing microneedles according to the present invention uses a specific combination of a biodegradable polymer, a stabilizer and an antioxidant to prevent the denaturation of the active ingredient liraglutide during the manufacture of microneedles and to ensure that the stability of liraglutide is maintained after the manufacture of microneedles.

The application provides a kind of targeted self-driven nanomotor hydrogel and its preparation method and application, belong to the field of biological medicine. Including the following steps: Janus mesoporous silica platinum nanomotor is synthesized by Pickering emulsion method, first loaded liraglutide by amination reaction, then grafted rapeseed DPP-IV inhibiting peptide by amide method, and encapsulated in sodium alginate microspheres, to obtain self-driven nanomotor hydrogel. The self-driven nanomotor described in the application can actively overcome the intestinal mucus barrier, pass through the mucus barrier into the specific site by autonomous navigation, significantly enhance the drug efficiency, avoid degradation in harsh stomach environment, reverse insulin resistance, reduce inflammatory complications such as diabetes, and enhance the safety and bioavailability of drugs.

The present invention relates to a method for administration of peptide drugs via a reusable pen comprising a replaceable drug cartridge. In particular, the present invention relates to a liraglutide solution administered via a reusable pen. Further, the present invention relates to a semaglutide solution administered via a reusable pen. Further, the present invention also relates to a tirzepatide solution administered via a reusable pen. Further, the present invention also relates to a setmelanotide solution administered via a reusable pen. Further, the present invention also relates to a teduglutide solution administered via a reusable pen.

The invention provides a method for detecting drug residues in excrement of rodent experimental animals, relates to the technical field of animal experimental analysis, and aims at detecting drugs such as baicalin and liraglutide. The method comprises the following steps: firstly, dividing experimental animals into six groups (including blank groups), collecting excrement at the time period of 4 hours before administration and 4 hours after administration, deodorizing by using activated carbon with specific specifications, transporting at the temperature of less than or equal to 4 DEG C (less than or equal to 3 hours), and storing at the temperature of-70 DEG C (less than or equal to 6 months); the baicalin is subjected to low-temperature and low-pressure drying (the temperature is lower than 55 DEG C, and the negative pressure is not less than 0.2 kPa), the liraglutide is subjected to low-temperature freeze drying (the temperature is lower than 30 DEG C), and the water content of a sample is controlled to be smaller than or equal to 1%; finally, after pretreatment with a corresponding solvent, LC-MS is used for detection. The method shortens the contact time of personnel and excrement, reduces the infection risk, improves the authenticity and stability of detection data, and is suitable for pharmacokinetic and toxic experiments.

The present invention provides a method for producing a peptide having the sequence His-X-Glu-Gly-Thr-Phe-Thr, comprising enzymatically coupling (a) a peptide C-terminal ester or thioester comprising a first peptide fragment having the sequence His-X-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-(thio)ester with (b) a peptide nucleophile having an N-terminal unprotected amine comprising a second peptide fragment having the sequence H-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Y-Glu-Phe-Ile-Ala-Trp-Leu-Val-Z-Gly-Arg-Gly. a method for synthesizing a peptide comprising: -Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Y-Glu-Phe-Ile-Ala-Trp-Leu-Val-Z-Gly-Arg-Gly, wherein X is Ala or an α-amino-isobutyric acid (Aib) residue; Y is Lys having a free side chain ε-amino group or the side chain ε-amino group of Lys is protected by a protecting group or the side chain ε-amino group of Lys is functionalized with an amino acid or another functional group; and Z is Arg or Lys.

The disclosure relates to a method of treating cancer by administering to an overweight human subject at least one glucagon-like peptide-1 receptor agonist (GLP-1RA) and at least one immune checkpoint inhibitor. The disclosure also relates to a method for treating an overweight human subject having cancer by administering the subject a therapeutically effective combination of at least one GLP-1RA and at least one immune checkpoint inhibitor. The method may also reduce resistance to immune checkpoint inhibition. The cancer being treated may be non-small cell lung cancer, including non-small cell lung cancer that is resistant to immune checkpoint inhibition. The GLP-1RA may be liraglutide or semaglutide and the immune checkpoint inhibitor may be pembrolizumab.

The invention relates to a cation exchange chromatographic analysis method of GLP-1 polypeptides, and belongs to the technical field of polypeptide drug analysis. According to the method, a cation exchange chromatographic column is adopted, a mobile phase system consisting of an acidic phosphate buffer solution phase A, a mixed solution phase B of a weakly acidic or weakly alkaline phosphate buffer solution and a sodium chloride solution and a methanol phase C is used, and detection is carried out under the wavelength of 210 nm through a specific gradient elution procedure. In the method, the pH value of an acidic phosphate buffer solution is 2.0-3.0, the pH value of a weakly acidic or weakly alkaline phosphate buffer solution is 6.0-8.0, and the flow velocity of a mobile phase is 0.5-1.5 mL / min. The invention also provides a sample pretreatment method, i.e., pH gt is used; and 7.5, dissolving the sample by using a phosphate buffer solution. The method is applicable to detection of GLP-1 polypeptides such as semeglutide and liraglutide and impurities thereof, has the advantages of high specificity, good separation effect, high repeatability and low detection limit, and can effectively solve the problem of lack of analysis methods for detecting GLP-1 polypeptides and impurities by using different principles in the prior art.

This invention discloses a strain of *Lactobacillus delbrueckii* with muscle-protecting function during fat loss, its products, and applications, belonging to the field of microbial technology. The invention discloses *Lactobacillus delbrueckii* subspecies Turb8, with accession number CGMCC No. 35627. This strain or its preparations can effectively prevent or improve muscle loss and functional decline during the use of fat-loss drugs such as GLP-1 receptor agonists (e.g., liraglutide, smegglutide), achieving the effect of "fat loss without muscle loss." While maintaining the original weight-loss effect of fat-loss drugs, the strain of this invention can significantly increase the user's lean body mass percentage, increase lower limb muscle mass, increase muscle fiber cross-sectional area, and improve muscle function indicators such as limb strength and suspension endurance. This invention also relates to bacterial agents containing this strain, various preparations, and their application in the preparation of products for improving (especially drug-induced) muscle loss.

The present invention relates to a method for preparing a glucagon-like peptide by precipitating the peptide or precursor peptide by mixing with an anti-solvent comprising diisopropyl ether and acetonitrile. Furthermore, the present invention relates to a peptide conjugated to a solid phase and a pharmaceutical composition comprising liraglutide obtainable according to the method of the present invention.

The present invention provides a composition for manufacturing liraglutide-containing microneedles that contains liraglutide as an active ingredient, without denaturation of the active ingredient during manufacture, and maintains stability even after manufacture, and liraglutide-containing microneedles with enhanced stability manufactured using the composition. The composition for manufacturing liraglutide-containing microneedles according to the present invention uses a specific combination of a biodegradable polymer, a stabilizer and an antioxidant to prevent the denaturation of the active ingredient liraglutide during the manufacture of microneedles and to ensure that the stability of liraglutide is maintained after the manufacture of microneedles.